Psoriasis is a debilitating autoimmune dermatological disease that affects about 2.6% of the population. Plaque psoriasis, the most common form of the disease, is characterized by red skin covered with silvery scales. Histologically the picture is one of disordered differentation and hyperproliferation of keratinocytes within the psoriatic plaque with inflammatory cell infiltrates.
Onset occurs most often in early adult life, but also may begin in childhood or in aged people. Severity of the disease varies and is usually characterized by alternating periods of remission and flare-up. In more serious cases, psoriasis can affect up to 90% of the skin and can be life threatening.
New therapeutic agents are currently being developed to treat this skin disorder. Accurate, reliable, and appropriate documentation of the extent and severity of psoriasis is important in clinical practice, and essential for clinical trial research. In clinical trials, the objective quantification of the disease is critical to measure the efficacy of an investigational treatment by comparing the severity of disease before therapy to that measured after treatment. For a new therapy to achieve regulatory approval for marketing, its efficacy must be documented in clinical trials. Valid and reliable outcome measures are also important in evidence-based medicine to provide comparisons among similarly designed trials in the literature. Although outcome measures such as quality-of-life assessments are important methods of assessing patient morbidity and disease severity, the clinical evaluation of psoriasis severity currently is the primary efficacy variable in clinical trial research.
Despite the importance of psoriasis evaluation, there is a lack of consensus on the most appropriate measure.1-4 The measures most often employed in clinical trials to measure psoriasis disease severity are the Psoriasis Area and Severity Index (PASI) and the Psoriasis Global Assessment (PGA). PASI was developed in 1978 by Fredricksson and Pettersson5 for use in a single clinical trial. Subsequently, the PASI became popular as a research tool, but is not used in clinical practice. The PASI results in a single score for psoriasis severity from 0 to 72; the plaque qualities of erythema, infiltration, desquamation are weighted equally to each other in calculating the final score. The method for calculating such score is depicted in Table 1 below.
TABLE 1Method for calculating the Psoriasis Area and Severity Index (PASI)The original description of the PASI involves the assessmentover 4 body regions (head, trunk, upper and lower extremities) ofinfiltration, desquamation, and erythema, and body surface areainvolvement. The assessment for infiltration, desquamation, anderythema use a 5-point scale:No symptoms0Slight1Moderate2Marked3Very marked4Based on the extent of lesions in each anatomic region,the area affected is assigned a numerical value of 1 to 6:<10% of the body surface involved (per1region)10-29%230-49%350-69%470-89%590-100%6Since the head, upper extremities, trunk, and lower extremities, correspond to approximately 10, 20, 30, and 40% of body surface area, respectively, the PASI score can be calculated using the formula:PASI = 0.1 (Eh + Ih + Dh)Ah + 0.2(Eu + Iu + Du)Au + 0.3(Et + It + Dt)At + 0.4(El + Il + Dl)Alwhere E, I, D, and A denote the point score for erythema, infiltration, desquamation, and area, respectively, and h, u, t, and l denote head, upper extremities, trunk, and lower extremities, respectively. PASI varies in steps 0.1 units from 0.0 to 72.0, with the highest score representing near or complete body involvement with the most severe erythema, infiltration, and desquamation possible.
The PGA allows the investigator to assign a single estimate of the patient's overall severity of disease; typically, a 7-point scale from clear to severe is used, although many variations have been employed. The PGA evaluates disease severity in a more intuitive and clinically meaningful way than does the 0 to 72 score of the PASI. In most versions of the PGA, the individual elements of psoriasis plaque morphology or degree of body surface area involvement are not quantified. A detailed description of one PGA method is depicted in Table 2 below.
TABLE 2Description of a Physician's Global Assessment (PGA)SevereVery marked plague elevation, scaling, and/or erythemaModerateMarked plaque elevation, scaling, and/or erythemato severeModerateModerate plague elevation, scaling, and/or erythemaMild toIntermediate between moderate and mildmoderateMildSlight scaling plaque elevation, scaling, and/or erythemaAlmostIntermediate between mild and clearclearClearNo signs of psoriasis (post-inflammatory hyperpigmentationmay be present)
The reliability of current clinical outcome measures is uncertain. Accordingly, new methods for rating the severity of psoriasis are needed.